Biomedical subjects

Deanna K Greenstein

Publications and source records attributed to Deanna K Greenstein.

10 recordsLinked to original sources

PubMed2006

Sleep disturbances in childhood-onset schizophrenia.

Sleep disturbances in psychiatric disease have long been reported. However, research on sleep disturbances in child and adolescent psychiatric disorders is limited. We examined the relationship of sleep disturbance to clinical severity and co-morbid diagnoses (e.g. anxiety), for a population with childhood-onset schizophrenia (COS). Sixty-one COS patients underwent a medication-free inpatient observation period as part of an NIMH study of COS. Sleep quantity during the last 5-7 days of a patient's medication-free period was measured using safety records and daily nursing notes. Subjects were divided into two groups: "good sleepers" (>6 h) and "poor sleepers" (<6 h) based on the average of total hours slept per night. Comparisons between groups were made with respect to clinical ratings at both admission and during washout period, co-morbid diagnosis of generalized anxiety disorder (GAD) and a susceptibility gene (G72) for COS. The median average sleep score for the entire group was 6.1 (S.D.=2.01) h. The good and poor sleep groups differed significantly in terms of severity of positive symptoms (SAPS) and negative symptoms at admission (SANS) both on admission and during the medication-free period. There was no significant relationship between G72 genotypes and a past and/or present diagnosis of GAD. COS patients suffer from significant sleep disturbances and the sleep disturbance is highly related to the symptom severity. As there are numerous health implications of poor sleep, clinicians should have a low threshold for treating sleep disturbances in this population.

Adolescent↗

PubMed2006

Mapping anatomical correlations across cerebral cortex (MACACC) using cortical thickness from MRI.

We introduce MACACC-Mapping Anatomical Correlations Across Cerebral Cortex-to study correlated changes within and across different cortical networks. The principal topic of investigation is whether the thickness of one area of the cortex changes in a statistically correlated fashion with changes in thickness of other cortical regions. We further extend these methods by introducing techniques to test whether different population groupings exhibit significantly varying MACACC patterns. The methods are described in detail and applied to a normal childhood development population (n = 292), and show that association cortices have the highest correlation strengths. Taking Brodmann Area (BA) 44 as a seed region revealed MACACC patterns strikingly similar to tractography maps obtained from diffusion tensor imaging. Furthermore, the MACACC map of BA 44 changed with age, older subjects featuring tighter correlations with BA 44 in the anterior portions of the superior temporal gyri. Lastly, IQ-dependent MACACC differences were investigated, revealing steeper correlations between BA 44 and multiple frontal and parietal regions for the higher IQ group, most significantly (t = 4.0) in the anterior cingulate.

Adolescent↗

PubMed2005

Neurologic examination abnormalities in children with bipolar disorder or attention-deficit/hyperactivity disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BPD) are frequently comorbid and overlapping diagnoses. To move beyond diagnosis toward unique pathophysiology, we evaluated both ADHD and BPD children for neurologic examination abnormalities (NEAs) in comparison with normal control (NC) children. METHODS: We performed the Revised Physical and Neurological Examination for Soft Signs in three groups (ADHD, BPD, NC). Then, a rater blind to diagnosis evaluated their motor performance. Results were analyzed with a multiple analysis of covariance. RESULTS: Subjects with ADHD were impaired on repetitive task reaction time. In contrast, pediatric BPD subjects, both with and without comorbid ADHD, were impaired on sequential task reaction time. CONCLUSIONS: This differential pattern of NEAs by diagnosis suggests pathophysiologic differences between ADHD and BPD in children. Repetitive motor performance requires inhibition of nonrelevant movements; ADHD subjects' impairment in this domain supports the hypothesis that ADHD involves a core deficit of fronto-striato-basal ganglia neurocircuitry. In contrast, BPD subjects' impaired sequential motor performance is consistent with behavioral data showing impaired attentional set-shifting and reversal learning in BPD subjects. Further study, going beyond symptom description to determine pathophysiologic differences, is required to refine neuronal models of these often comorbid diagnoses.

Adolescent↗

PubMed2005

Support for association between ADHD and two candidate genes: NET1 and DRD1.

Attention deficit hyperactivity disorder (ADHD) is a common, multifactorial disorder with significant genetic contribution. Multiple candidate genes have been studied in ADHD, including the norepinephrine transporter (NET1) and dopamine D1 receptor (DRD1). NET1 is implicated in ADHD because of the efficacy of atomoxetine, a selective noradrenergic reuptake inhibitor, in the treatment of ADHD. DRD1 is primarily implicated through mouse models of ADHD. DNA from 163 ADHD probands, 192 parents, and 129 healthy controls was used to investigate possible associations between ADHD and polymorphisms in 12 previously studied candidate genes (5-HT1B, 5-HT2A, 5-HT2C, ADRA2A, CHRNA4, COMT, DAT1, DRD1, DRD4, DRD5, NET1, and SNAP-25). Analyses included case-control and family-based methods, and dimensional measures of behavior, cognition, and anatomic brain magnetic resonance imaging (MRI). Of the 12 genes examined, two showed a significant association with ADHD. Transmission disequilibrium test (TDT) analysis revealed significant association of two NET1 single nucleotide polymorphisms (SNPs) with ADHD (P < or = 0.009); case-control analysis revealed significant association of two DRD1 SNPs with ADHD (P < or = 0.008). No behavioral, cognitive, or brain MRI volume measurement significantly differed across NET1 or DRD1 genotypes at an alpha of 0.01. This study provides support for an association between ADHD and polymorphisms in both NET1 and DRD1; polymorphisms in ten other candidate genes were not associated with ADHD. Because family-based and case-control methods gave divergent results, both should be used in genetic studies of ADHD.

Adolescent↗

PubMed2005

Hormonal correlates of clozapine-induced weight gain in psychotic children: an exploratory study.

OBJECTIVE: Weight gain is a serious side effect of atypical antipsychotics, especially in childhood. In this study, the authors examined six weight gain-related hormones in patients with childhood-onset schizophrenia (COS) after 6 weeks of clozapine treatment. METHOD: Fasting serum samples for 24 patients with COS and 21 matched healthy controls (HC) were obtained. Levels of leptin, insulin, adiponectin, amylin, ghrelin, and tumor necrosis factor alpha were measured and compared between the groups. For 23 patients with COS, hormonal levels were measured at background and week 6 of clozapine treatment. Change in body mass index was correlated with levels of clozapine and changes in hormonal levels and clinical ratings. RESULTS: At baseline, COS did not differ significantly from HC on any hormonal measure. Clozapine treatment was associated with significant (7.9% +/- 8.5%) increase in mean body mass index. Only leptin levels increased significantly from baseline to week 6 on clozapine (p = .003). Body mass index increase was significantly correlated with decrease in ghrelin and adiponectin and was positively correlated with clinical improvement. CONCLUSIONS: This is the first study of weight gain-related hormones in children on clozapine. Hormonal changes are correlated with weight gain. How effectiveness of clozapine is linked to weight gain remains uncertain.

Adolescent↗

PubMed2004

Stimulant drug treatment in childhood-onset schizophrenia with comorbid ADHD: an open-label case series.

The administration of psychostimulants to children with psychotic symptoms is controversial. This study reports the stimulant drug response of 5 children, aged 8-15 years, with childhood-onset schizophrenia (COS) and comorbid attention deficit hyperactivity disorder (ADHD). Four COS inpatients were given stimulants for comorbid ADHD after stabilization of psychosis on antipsychotic medication. A fifth COS inpatient received stimulants while still actively psychotic, despite concurrent neuroleptic treatment. Data from the 10-item Brief Conners Teachers Ratings Scale (BCTRS) were examined the week before, and the week after, stimulant addition. A paired t test, conducted using Conners Teachers data from these 4 subjects, indicated significant improvement in ADHD symptoms (p = 0.02). Data obtained from a retrospective chart review indicated no significant worsening of psychosis. The 2 subjects treated with mixed salts of dextroamphetamine sulfate and amphetamine sulfate remained on that medication at 6 months and at the 2-year follow-up. Our results suggest that ADHD comorbid with COS may be safely treated with a stimulant, once the psychosis is stabilized. A systematic investigation of this question may be warranted.

Adolescent↗

PubMed2003

Monozygotic twins discordant for attention-deficit/hyperactivity disorder: ascertainment and clinical characteristics.

OBJECTIVE: Nongenetic factors and phenomenology of attention-deficit/hyperactivity disorder (ADHD) were examined in monozygotic (MZ) twin pairs discordant for ADHD. METHOD: Recruitment included telephone screening (n = 297 pairs), behavioral ratings obtained from parents and teachers (n = 59 pairs), and, finally, in-person assessment (n = 25 pairs; structured classroom observation, diagnostic interview, psychoeducational evaluation, birth record review, establishment of monozygosity, and anatomic brain imaging). Affected twins were further contrasted with previously studied affected singletons. RESULTS: Of the 25 MZ twin pairs qualifying for in-person evaluation, only 10 proved discordant for ADHD. Affected twins were mostly comparable with affected singletons on clinical measures, although fathers' self-ratings of childhood ADHD status were significantly lower in twins than in singletons. CONCLUSIONS: Discordance for ADHD in MZ twins appears to be ascribable to greater environmental discordance and decreased familiality. Despite these differences, affected twins were phenotypically comparable with affected singletons. Thus MZ twins discordant for ADHD, while rare, can inform research on the etiology and pathophysiology of this disorder.

Adolescent↗

PubMed2003

Progressive brain volume loss during adolescence in childhood-onset schizophrenia.

OBJECTIVE: Previous reports have documented a striking progressive reduction in cortical gray matter volume during adolescence in patients with childhood-onset schizophrenia. This study examined the rate of loss in cortical gray matter volume in relation to age and clinical status in adolescent patients over a follow-up period of 2-6 years. METHOD: A total of 131 brain magnetic resonance imaging scans were acquired for 60 subjects with childhood-onset schizophrenia (mean age=14.5 years, SD=2.5), and 140 scans were acquired for 64 matched healthy comparison subjects. One or more follow-up scans were acquired at approximately 2-year intervals for 39 subjects with childhood-onset schizophrenia and 43 healthy subjects. Developmental trajectories for total and regional brain volumes were examined in relation to age by using polynomial growth models and data from all available scans. The rate of gray matter reduction in patients with childhood-onset schizophrenia was examined in relation to developmental and clinical measures by using stepwise regression. RESULTS: Rates of brain volume reduction were significantly higher for patients with childhood-onset schizophrenia than for healthy comparison subjects. In childhood-onset schizophrenia, the rate of gray matter reduction was related to premorbid impairment and baseline severity of clinical symptoms but not to gender, ethnicity, or age at onset of the disorder. Unexpectedly, greater clinical improvement was significantly related to a higher rate of gray matter reduction. Longitudinal trajectories suggested that the rate of cortical loss plateaus during adolescence. CONCLUSIONS: Striking loss of cerebral gray matter is seen through adolescence in patients with childhood-onset schizophrenia. The rate of reduction was related to premorbid impairment and baseline symptom severity, but it may also be in part a plastic response to illness.

Adolescent↗

PubMed2003

Anatomic brain abnormalities in monozygotic twins discordant for attention deficit hyperactivity disorder.

OBJECTIVE: To examine brain-behavior relationships in attention deficit hyperactivity disorder (ADHD), the authors obtained magnetic resonance imaging (MRI) scans of monozygotic twins discordant for ADHD. METHOD: National recruitment was followed by in-person assessment. MRI scans were measured algorithmically for nine pairs of monozygotic twins discordant for ADHD. RESULTS: The affected twins had significantly smaller caudate volumes (mean difference=-0.56 ml, CI=-0.92 to -0.21) than their unaffected co-twins. CONCLUSIONS: These results provide further support for striatal models of ADHD pathophysiology.

Adolescent↗

PubMed2002

Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder.

CONTEXT: Various anatomic brain abnormalities have been reported for attention-deficit/hyperactivity disorder (ADHD), with varying methods, small samples, cross-sectional designs, and without accounting for stimulant drug exposure. OBJECTIVE: To compare regional brain volumes at initial scan and their change over time in medicated and previously unmedicated male and female patients with ADHD and healthy controls. DESIGN, SETTING, AND PARTICIPANTS: Case-control study conducted from 1991-2001 at the National Institute of Mental Health, Bethesda, Md, of 152 children and adolescents with ADHD (age range, 5-18 years) and 139 age- and sex-matched controls (age range, 4.5-19 years) recruited from the local community, who contributed 544 anatomic magnetic resonance images. MAIN OUTCOME MEASURES: Using completely automated methods, initial volumes and prospective age-related changes of total cerebrum, cerebellum, gray and white matter for the 4 major lobes, and caudate nucleus of the brain were compared in patients and controls. RESULTS: On initial scan, patients with ADHD had significantly smaller brain volumes in all regions, even after adjustment for significant covariates. This global difference was reflected in smaller total cerebral volumes (-3.2%, adjusted F(1,280) = 8.30, P =.004) and in significantly smaller cerebellar volumes (-3.5%, adjusted F(1,280) = 12.29, P =.001). Compared with controls, previously unmedicated children with ADHD demonstrated significantly smaller total cerebral volumes (overall F(2,288) = 6.65; all pairwise comparisons Bonferroni corrected, -5.8%; P =.002) and cerebellar volumes (-6.2%, F( 2,288) = 8.97, P<.001). Unmedicated children with ADHD also exhibited strikingly smaller total white matter volumes (F(2,288) = 11.65) compared with controls (-10.7%, P<.001) and with medicated children with ADHD (-8.9%, P<.001). Volumetric abnormalities persisted with age in total and regional cerebral measures (P =.002) and in the cerebellum (P =.003). Caudate nucleus volumes were initially abnormal for patients with ADHD (P =.05), but diagnostic differences disappeared as caudate volumes decreased for patients and controls during adolescence. Results were comparable for male and female patients on all measures. Frontal and temporal gray matter, caudate, and cerebellar volumes correlated significantly with parent- and clinician-rated severity measures within the ADHD sample (Pearson coefficients between -0.16 and -0.26; all P values were <.05). CONCLUSIONS: Developmental trajectories for all structures, except caudate, remain roughly parallel for patients and controls during childhood and adolescence, suggesting that genetic and/or early environmental influences on brain development in ADHD are fixed, nonprogressive, and unrelated to stimulant treatment.

Adolescent↗